Anesth Pain Med 2018;13:388-393 https://doi.org/10.17085/apm.2018.13.4.388 pissn 1975-5171 ㆍ eissn 2383-7977 임상연구 수면심도를달리하여전신마취를받는환자에서처리해리절차를이용한기억형성평가 정유리 1 ㆍ최병문 1 ㆍ노규정 1,2 울산대학교의과대학서울아산병원 1 마취통증의학교실, 2 임상약리학교실 Received April 3, 2018 Revised 1st, May 19, 2018 2nd, May 30, 2018 Accepted May 30, 2018 Investigation into memory formation according to the level of hypnotic depth using process dissociation Yu-Ri Jung 1, Byung-Moon Choi 1, and Gyu-Jeong Noh 1,2 Departments of 1 Anesthesiology and Pain Medicine, 2 Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Corresponding author Byung-Moon Choi, M.D., Ph.D. Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Tel: 82-2-3010-1704 Fax: 82-2-3010-6790 E-mail: byungmoonchoi7@gmail.com ORCID http://orcid.org/0000-0002-6561-8851 Background: Process dissociation procedure has been used to evaluate explicit and implicit memories. Two process-dissociation measurement models are described. Methods: This prospective study evaluated intraoperative memory formation in Korean patients undergoing elective surgery under general anesthesia and its relation to the depth of hypnotic state. A total of 270 patients enrolled were randomly assigned to three groups based on Bispectral Index (BIS) values in the following ranges: 30 to 40, BIS 40 to 50, and BIS 50 to 60 according to the level of hypnotic depth induced by propofol or sevoflurane during the presentation of wordlists. When the level of hypnotic depth was maintained at the target BIS range, words were played for 15 minutes via headphones to patients. Within 24 hours after the word presentation, memory was assessed using an auditory word stem completion test. The probability of explicit and implicit memory was calculated using original and extended measurement models. Brice interviews were performed within 1 and 24 hours after surgery. Results: A total of 119 patients who did not deviate from the target BIS range were included in the analysis. The 95% confidence interval (CI) of the probability of occurrence of implicit memory evaluated by the original model did not include zero. However, when the extension model was used, 0 was included in the 95% CI. Explicit memory evaluated via Brice interviews did not occur in any group. Conclusions: When BIS was maintained in the range of 30 to 60 during surgery, no explicit or implicit memory was observed. Keywords: Anesthesia; Intraoperative awareness; Memory. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright c the Korean Society of Anesthesiologists, 2018 388
처리해리절차를이용한기억형성평가 서 론 대상및방법 전신마취를받는환자에서기억형성이일어나지않도록수술중적절한수면심도를유지시켜주는것은중요하다. 전신마취과정에서발생할수있는기억은그것을의식적으로회상할수있는지여부에따라외현기억 (explicit memory) 또는암묵기억 (implicit memory) 으로나눌수있다 [1]. 외현기억은수술중에일어난사건을의식적인통제처리에의하여명확하게기억하는것을의미하며, 기억의형성과정에서회상 (recollection) 에해당하며 [1,2], 수술중각성은외현기억과직접적으로연관된다 [3]. 반면암묵기억은무의식적인자동처리로명확하게기억할수는없지만, 수술후행동변화등을일으킬수있는기억으로, 기억의형성과정에서친숙기억 (familiarity) 에해당한다 [1,2]. 전신마취를받는환자에서외현기억발생여부를확인하는방법은수술후에설문을통하여확인할수있다 [4]. 그렇지만암묵기억의발생은설문을통한환자의답변만으로는파악할수가없다. 이를해결하기위하여미국의인지심리학자인 Jacoby [2] 가기억에미치는무의식적인자동처리와의식적인통제처리의영향을수학적으로분리해낼수있는처리해리절차 (process dissociation procedure) 를제안하였다. 처리해리절차는외현기억과암묵기억의발생여부를분리해서평가하는실제적인방법으로단어완성검사 (word-stem completion test) 를활용한다 [2]. 수술중에특정한단어를반복적으로들려주고, 수술후에의식적으로혹은무의식적으로그단어들을기억해낼수있는지를평가하는방법이다. 이방법을활용하여실제임상에서다양한환자군을대상으로외현, 암묵기억발생여부가평가되었다 [5 8]. 이후정신과의사인 Buchner 등 [9] 이외현, 암묵기억을계산할때우연히단어를맞출경우를고려해야한다고주장하며, 본인의계산과정을 Jacoby의원래모형 (original model) 과구분하기위하여확장모형 (extended model) 으로발표하였다. 이확장모형을이용하여정례수술을받는환자집단을대상으로그집단에서외현, 암묵기억발생여부를파악하는연구도수행된바가있다 [10]. 국내에서도처리해리절차를이용하여제왕절개를받는산모를대상으로외현기억과암묵기억의발생여부를평가한연구가있지만 [11], 원래모형으로만발생여부를판단하고, 확장모형을적용하지는않았다. 또한, 수술중허용가능한수면심도범위를세분화하여외현기억과암묵기억의발생을연구할필요성도있다. 본연구의목적은정례수술로전신마취를받는환자를대상으로하여마취의심도를다양하게유지하면서단어완성검사를시행하고, 이를근거로하여원래모형과확장모형으로마취중외현기억과암묵기억의발생여부를확인해보고자한다. 본연구는서울아산병원의임상연구심의위원회 ( 승인번호. 2012-0865) 의승인을받은후전신마취로정례수술을받는미국마취과학회신체등급분류 1, 2인만 20세이상의수술환자 270명을대상으로서면동의를획득한후에시행되었다. 한국어를모국어로사용하고있으며, 최종학력이고등학교졸업이상인환자를대상으로하였고, 문맹이거나청력장애가있는환자는연구에서제외하였다. 환자가수술실에도착하면심전도, 비침습적혈압계및맥박산소포화도계측기 (Datex-Ohmeda S/5, Planar Systems, Inc., USA) 를거치하고, 이마에바이스펙지수 (BIS TM VISTA monitoring system, Covidien, USA) 센서를거치하였다. 바이스펙트럼지수 (Bispectral Index, BIS) 값은 RS232C 케이블을이용하여후향적분석을위하여개인용컴퓨터에다운로드받았다. 마취유도는 propofol을 2 mg/kg 단회정주하였고, 마취유지는 Schnider 모형을이용하여 propofol을목표효과처농도조절주입하거나 [12], sevoflurane을이용하였다. Remifentanil 은 Minto 모형을이용하여 2 20 ng/ml 범위에서목표효과처농도조절주입을시행하였다 [13]. Propofol과 remifentanil 의목표농도조절주입을위하여주입펌프 (Perfusor Space, B. Braun, Germany) 를이용하였다. 마취유도과정에서 눈떠보세요 라는구두명령에환자분이반응하지않는것을확인한이후에신경근차단제인 rocuronium 0.6 mg/kg를정주하고, 사연속자극 (train-of-four) 으로감시한손가락움직임반응이 2 개이하일때기관내삽관을시행하였다. 수술중목표 BIS 범위를유지하기위하여 propofol의목표효과처농도는 2 5 mg/ml 를유지하였고, sevoflurane의호기말농도는 1.5 4 vol% 를유지하였다. 안정적인혈압 ( 수축기혈압 > 80 mmhg, 심박수 > 45 beats/min) 을유지하기위하여필요할경우 ephedrine과 atropine을정주하였다. 환자들에게는수술중단어목록을헤드셋을이용하여들려주었으며, 단어목록을들려주는기간동안유지하는수면심도에따라 BIS를 30에서 40 사이로유지하는군 (BIS 30 40), 40에서 50 사이로유지하는군 (BIS 40 50), 50에서 60 사이로유지하는군 (BIS 50 60) 으로무작위배정하였다. 수술이진행되어수술적자극의변동이심하지않은시점에서, 목표 BIS 범위가유지되는것을확인한이후에선정한단어목록을들려주었다. 20대초반의여성의목소리로 MP3 파일형태로녹음된단어목록을반복하여 15분동안들려주었다. 본연구에사용한단어목록은 24개의단어를 6개씩 4개의목록으로나누었으며, 그단어목록은다음과같다. ㆍ목록 1: 시대, 교수, 과거, 처녀, 미소, 비서ㆍ목록 2: 나무, 바다, 버스, 허리, 고기, 후보 KSAP www.anesth-pain-med.org 389
Anesth Pain Med Vol. 13 No. 4 ㆍ목록 3: 자유, 가지, 차이, 회의, 커피, 세포ㆍ목록 4: 노래, 구두, 조사, 어제, 우주, 치마단어목록에포함되어있는각각의단어는명사이고반드시종성이없는, 즉받침이없는 2음절의단어만을사용하였으며연세대학교언어정보연구원의현대한국어의어휘빈도에따른사용빈도가 100만단어당 400번이상의사용빈도를가진단어로이전연구에서사용한것을활용하였다 [11]. 수술후에이루어지는단어완성검사에서는포섭조건에두개의단어목록을사용하여그중하나는포섭제시 (inclusion target) 단어목록으로나머지하나는포섭비제시 (inclusion distractor) 단어목록으로이용하고, 배제조건에또한두개의단어목록을사용하여그중하나는배제제시 (exclusion target) 단어목록으로나머지하나는배제비제시 (exclusion distractor) 단어목록으로이용한다. 여기에서포섭조건, 배제조건, 제시단어, 비제시단어의의미는다음과같다. ㆍ 포섭조건 : 수술장에서들려준단어가기억이나거나제일처음떠오르는단어ㆍ 배제조건 : 수술장에서들려준단어가기억나면이를배제하고, 기억이나지않으면제일처음떠오르는단어ㆍ 제시단어 : 수술장에서들려준단어ㆍ 비제시단어 : 수술장에서들려주지않은단어예를들어수술장에서는단어목록 1과 3을들려주고, 수술후단어완성검사때에는단어목록 1 4 까지의모든단어의첫음절을들려주는데, 단어목록 1과 2를들려줄때에는, 수술중들었던단어가기억이나거나제일처음떠오르는단어를적으라고제시하고, 단어목록 3과 4를들려줄때에는수술장에서들려준단어가기억나면이를배제하고적고, 기억나지않으면그냥제일처음떠오르는단어를적으라고제시한다. 이럴경우단어목록 1은포섭제시단어목록이되고, 단어목록 2는포섭비제시단어목록이된다. 단어목록 3은배제제시단어목록이되고, 단어목록 4는배제비제시단어목록이된다. 또한, 각각의단어목록을균등하게사용하기위하여포섭제시단어목록, 포섭비제시단어목록, 배제제시단어목록, 배제비제시단어목록을무작위배정하는 counterbalancing schema를사용하였다 [11]. 수술이종료된후환자의의식이회복되어, 설문에응답할수있을때회복실에서 Brice 인터뷰를진행하였다 [4]. 인터뷰항목은다음의 5가지질문으로구성하였다. ㆍ 수술실에서잠들기전에마지막으로기억나는것이무엇입니까? ㆍ 수술후에제일처음기억나는것이무엇입니까? ㆍ 수술을받는동안기억나는것이무엇입니까? ㆍ 수술을받는동안혹시꿈을꾸셨다면어떤꿈이었습니까? ㆍ 수술과관련하여가장끔찍한것이무엇입니까? 인터뷰에응답한내용은 Michigan 각성분류체계에따라서 평가하였다 [14]. 단어완성검사는수술종료후 24시간이내에병실에서진행하였고, 단어완성검사후 Brice 인터뷰를한번더진행하였다. 단어완성검사자료를이용하여외현기억과암묵기억이발생할확률을계산하는처리해리절차는측정모형에따라서달라진다 [10]. 원래모형을이용하면다음식으로계산할수있다 [2]. C = TI TE (1) A = TE 1 C (2) 여기에서 C는외현기억이발생할확률이고, A는암묵기억이발생할확률이다. TI는포섭조건에서단어를맞출확률이고, TE 는배제조건에서단어를맞출확률이다. 반면에확장모형을이용할경우다음식을이용한다 [9]. 1 G TI i (TE G 1 G e ) G i C = e 1 + G e 1 G (3) i G 1 G i e A = TE 1 C G e 1 G e (4) 여기에서 G i 는포섭조건에서우연히제시어를맞출확률이며, G e 는배제조건에서우연히제시어를맞출확률이다. 전체집단의환자에서외현기억과암묵기억이발생할확률의 95% 신뢰구간을각각구하고, 그신뢰구간에 0이포함되면기억이발생하지않는것으로, 0을포함하지않으면서발생확률이양의값을가질경우기억이발생한것으로해석한다. 결 과 본연구에참여하기로서면동의한 270명의환자중에서분석에포함된환자수는 119명이었다. 151명이배제되었는데, 주된이유는단어완성검사를위하여수술중에 15분동안단어목록을들려주는동안목표로설정한 BIS 범위를벗어난경우가발생하였기때문이었다. 기타배제된이유및무작위배정결과에대한보다상세한내용은 Fig. 1에제시하였다. 분석에포함된환자들의신체특성은군간에유의한차이는관찰되지않았다 (Table 1). 각군간에수술중단어목록을들려주는동안유지된개인별평균 BIS의분포를 Fig. 2에나타내었다. 동일한목표효과처농도를유지한다고하더라도 BIS 값이일정한값으로유지되지는않기때문에목표 BIS 범위내로 BIS 값을 15분동안유지하는것이현실적으로어려워서, 중도탈락한환자들이많이발생하였다. 분석에포함된환자들은단어목록을들려주는동안목표 BIS 범위내로 BIS 값이유지가잘되었다. 390 www.anesth-pain-med.org
처리해리절차를이용한기억형성평가 Assessed for eligibility (n =275) Exculded (n = 5) Violation of inclusion criteria Enrolled (n =270 ) Analyzed (n =119) Excluded (n = 151) Withdrawal of consent (n = 10) Refusal to perform word-stem completion test (n = 5) Changes in the operation schedule (n = 10) Deviation of BIS values allowed by the protocol (n = 126) KSAP BIS: 30 40 (n =37) BIS: 40 50 (n =51) BIS: 50 60 (n =31) Fig. 1. CONSORT diagram of participants. BIS: Bispectral Index. Table 1. Patient Characteristics (n = 119) Variable BIS 30 40 (n = 37) BIS 40 50 (n = 51) BIS 50 60 (n = 31) Weight (kg) 61.3 ± 11.8 62.4 ± 12.1 63.4 ± 11.5 Height (cm) 162.8 ± 8.6 163.0 ± 9.4 165.4 ± 7.5 Age (yr) 44.2 ± 9.5 42.7 ± 9.2 42.5 ± 10.1 Sex (M/F) 10/27 15/36 8/23 ASA PS (I/II) 15/22 22/29 12/19 Highest level of education High school 12 19 11 College or university 24 30 18 Graduate school 1 2 2 Duration of anesthesia (min) 120.0 (103.5 167.5) 125.0 (106.3 165.0) 120.0 (106.3 162.8) Hypnotic agents administered during surgery Propofol 9 19 8 Sevoflurane 28 32 23 Operation BE 21 32 18 ST 9 13 6 CRS 7 6 7 Values are presented as mean ± SD, number or median (25 75%). ASA PS: American Society of Anesthesiologists physical status classification, BE: breast and thyroid surgery including breast conservation operation, modified radical mastectomy and total thyroidectomy, ST: stomach surgery including distal or total gastrectomy, CRS: colorectal surgery including right hemicolectomy, anterior resection, low anterior resection, and ileocecal resection. A 60 B 60 C 60 BIS 50 40 30 0 BIS 50 40 30 5 10 15 0 Time (min) BIS 50 40 30 5 10 15 0 Time (min) 5 10 Time (min) 15 Fig. 2. Time courses of Bispectral Index (BIS) during the presentation of the word lists to the patients assigned to three groups based on target BIS. (A) BIS 30 40, (B) BIS 40 50, (C) BIS 50 60. 원래모형과확장모형으로처리해리절차를이용하여외현기억 과암묵기억이발생할확률을계산하였고, 이를 Table 2에제시하였다. 원래모형으로평가한경우에는모든군에서외현기억은 발생하지않았지만암묵기억은발생하였고, 확장모형으로평가한경우에는모든군에서외현기억과암묵기억이발생하지않았다. 포섭조건과배제조건에서단어를맞춘개수는군간에통계 www.anesth-pain-med.org 391
Anesth Pain Med Vol. 13 No. 4 Table 2. Probability of Target Completion based on Explicit Memory and Implicit Memory Calculated using Two Different Measurement Models of Process Dissociation Procedure Model BIS 30 40 (n = 37) BIS 40 50 (n = 51) BIS 50 60 (n = 31) Explicit memory Original model 0.03 ( 0.03, 0.09) 0.00 ( 0.06, 0.06) 0.07 ( 0.01, 0.14) Extended model 0.00 ( 0.08, 0.08) 0.05 ( 0.17, 0.06) 0.03 ( 0.08, 0.14) Implicit memory Original model 0.12 (0.07, 0.16) 0.15 (0.12, 0.19) 0.14 (0.08, 0.19) Extended model 0.09 ( 0.18, 0.01) 0.05 ( 0.12, 0.02) 0.06 ( 0.17, 0.05) Values are presented as mean (95% confidence interval). Original model and extended model were the calculation methods proposed by Jacoby and Buchner, respectively [2,9]. 적인차이가나지는않았다 (Kruskal-Wallis One Way Analysis of Variance on Ranks, P = 0.244, P = 0.365). Brice 인터뷰결과에서도외현기억은발생하지않았다. 고찰 수세기에걸쳐기억은시인과철학자, 과학자들을매료시켜왔다. 기억은경험에의한행동양상의변화로대변되며, 사회와문화의발전뿐아니라자아에대한인식측면에서도중요하다. 이런관점에서예전부터기억은철학자들의영역이었다. 플라톤은그의저서테아이테토스 (Theatetus) 에서생각들은기억으로새겨진다고하였다. 기억에대한실험적연구는 19세기에시작되었으며, 그당시에여러신경과의사들과정신과의사들이기억기능에이상이있는환자들을인식하기시작하였고, 여러심리학자들은기억의종류와단계에대해정의하기시작하였다. 무의식적인자동처리과정에의하여기억되는암묵기억은자전거타기나거울보고그리기와같은절차기억을포함한다 [1]. 반면의식적인통제처리에의하여명확하게기억하는외현기억은의미론적 (semantic) 기억과일화적 (episodic) 기억을포함한다. 의미론적기억은특정시점이나맥락과연합되어있지않은세상의다양한대상, 사물또는현상에관하여일반적인지식형태로저장되어있는기억을지칭하며, 일화적기억은의미론적기억과달리시간및장소와관련되어조직된기억내용을지칭한다 [1]. 기억에미치는무의식적인자동처리와의식적인통제처리의영향을수학적으로분리해낼수있는처리해리절차가제안된이후로 [2], 이를활용하여마취제의종류와다양한수술종류에대하여수술중외현, 암묵기억의발생여부를규명한연구가진행되었다 [5 8]. 외상환자를대상으로평가한선행연구에서는 BIS 40 60에서암묵기억이발생할수있으며, 기억이수면심도 (depth of hypnosis) 와관련이있음을제시하였다 [5]. 또한, 제왕절개수술을받는환자를대상으로시행한연구에서도단어를들려주는동안의평균 BIS가 76.3인상태의비교적얕은수면심 도상태에서환자들은포섭 (inclusion) 과배제 (exclusion) 를정확하게결정할수있었으며, 의식적회상 (conscious recall) 없이도외현기억이발생할수있다고제시하였다 [6]. 정례수술환자를대상으로 propofol과 isoflurane을무작위배정하여진행한연구에서는적절한수면심도가유지된다면기억형성을차단하는데두마취제는동일한효과를발휘한다고보고되기도하였다 [7]. 정례수술을받는환자를대상으로수면심도수준을달리하면서각수면심도수준에서각기다른단어를들려주면서원래모형으로평가한결과 BIS 21 40, 41 60, 61 80 범위에서모두암묵기억이발생하였음이보고되었는데 [8], 이는확장모형으로재분석할경우모든군에서암묵기억이발생하지않는다는상반된결과가나왔다 [10]. 또한, 수술중암묵기억이발생한다고밝힌다른선행연구를대상으로 [6,15,16], 확장모형으로자료를재분석할경우암묵기억이발생하지않는다는보고도있다 [10]. 이는이번연구결과와도일치하는견해이다. 결국확장모형은우연에의하여단어를맞출가능성을외현, 암묵기억계산과정에반영함으로써암묵기억으로오인될수있는부분을적절하게차단시켜준것으로해석할수있다. 암묵기억이임상적으로의미를갖는이유는무의식적인자동처리로명확하게기억할수는없지만, 수술후행동변화등을일으킬수있어외상후스트레스장애를초래할수도있기때문이다 [17]. 이연구의제한점은높은중도탈락률로인하여군간의분석대상자수에차이를보여서, 수면심도에따른외현, 암묵기억의발생이차이를보이는지를탐색하는데불충분한표본수를확보하였을수도있다는점이다. 그렇지만선행연구에서군내 12명내지는 30명의연구참여자를대상으로결과를제시한문헌도있을뿐더러 [18,19], 본연구의결과가그동안진행되어온일련의처리해리절차를이용한선행연구와도일치하는소견이어서본연구에서의결과를수용하는데크게무리는없을것으로판단한다. 결론적으로수면심도를 BIS 30 60으로유지할경우에원래모형으로평가할경우외현기억은발생하지않고, 암묵기억은발생하지만, 확장모형으로평가할경우외현기억과암묵기억모두 392 www.anesth-pain-med.org
처리해리절차를이용한기억형성평가 발생하지않았다. 따라서통상의진료지침대로수면심도를 BIS 60 미만으로유지할경우암묵기억은발생하지않는것으로간주할수있다. 감사의글 This study was supported by grant (2012-0865) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea. REFERENCES 1. Squire LR, Zola SM. Structure and function of declarative and nondeclarative memory systems. Proc Natl Acad Sci U S A 1996; 93: 13515-22. 2. Jacoby LL. A process dissociation framework: separating automatic from intentional uses of memory. J MEM LANG 1991; 30: 513-41. 3. Ghoneim MM. Awareness during anesthesia. Anesthesiology 2000; 92: 597-602. 4. Brice DD, Hetherington RR, Utting JE. A simple study of awareness and dreaming during anaesthesia. Br J Anaesth 1970; 42: 535-42. 5. Lubke GH, Kerssens C, Phaf H, Sebel PS. Dependence of explicit and implicit memory on hypnotic state in trauma patients. Anesthesiology 1999; 90: 670-80. 6. Lubke GH, Kerssens C, Gershon RY, Sebel PS. Memory formation during general anesthesia for emergency cesarean sections. Anesthesiology 2000; 92: 1029-34. 7. Kerssens C, Ouchi T, Sebel PS. No evidence of memory function during anesthesia with propofol or isoflurane with close control of hypnotic state. Anesthesiology 2005; 102: 57-62. 8. Iselin-Chaves IA, Willems SJ, Jermann FC, Forster A, Adam SR, Van der Linden M. Investigation of implicit memory during isoflurane anesthesia for elective surgery using the process dissociation procedure. Anesthesiology 2005; 103: 925-33. 9. Buchner A, Erdfelder E, Vaterrodt-Plünnecke B. Toward unbiased measurement of conscious and unconscious memory processes within the process dissociation framework. J Exp Psychol Gen 1995; 124: 137-60. 10. Hadzidiakos D, Horn N, Degener R, Buchner A, Rehberg B. Analysis of memory formation during general anesthesia (Propofol/ Remifentanil) for elective surgery using the process-dissociation procedure. Anesthesiology 2009; 111: 293-301. 11. Jeon WJ, Noh GJ, Shim JH, Cho SY, Yeom JH, Shin WJ, et al. The assessment of explicit memory and implicit memory after general anesthesia for cesarean section using the process dissociation procedure. Korean J Anesthesiol 2003; 45: 78-86. 12. Schnider TW, Minto CF, Gambus PL, Andresen C, Goodale DB, Shafer SL, et al. The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers. Anesthesiology 1998; 88: 1170-82. 13. Minto CF, Schnider TW, Egan TD, Youngs E, Lemmens HJ, Gambus PL, et al. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology 1997; 86: 10-23. 14. Mashour GA, Esaki RK, Tremper KK, Glick DB, O'Connor M, Avidan MS. A novel classification instrument for intraoperative awareness events. Anesth Analg 2010; 110: 813-5. 15. Stapleton CL, Andrade J. An investigation of learning during propofol sedation and anesthesia using the process dissociation procedure. Anesthesiology 2000; 93: 1418-25. 16. Kerssens C, Lubke GH, Klein J, van der Woerd A, Bonke B. Memory function during propofol and alfentanil anesthesia: predictive value of individual differences. Anesthesiology 2002; 97: 382-9. 17. Zeitlin SB, McNally RJ. Implicit and explicit memory bias for threat in post-traumatic stress disorder. Behav Res Ther 1991; 29: 451-7. 18. Tian SY, Zou L, Quan X, Zhang Y, Xue FS, Ye TH. Effect of midazolam on memory: a study of process dissociation procedure and functional magnetic resonance imaging. Anaesthesia 2010; 65: 586-94. 19. Quan X, Yi J, Ye TH, Tian SY, Zou L, Yu XR, et al. Propofol and memory: a study using a process dissociation procedure and functional magnetic resonance imaging. Anaesthesia 2013; 68: 391-9. KSAP www.anesth-pain-med.org 393